The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously sensitized food allergy.

Cutaneous sensitization with a food antigen before its consumption elicits the development of food allergy. Here, we report the site- and stage-dependent roles of basophils and proallergic cytokines, thymic stromal lymphopoietin (TSLP) and IL-33, in a mouse model of food allergy initially sensitized cutaneously with the food antigen. Mice were epicutaneously sensitized with the food antigen ovalbumin (OVA) followed by oral challenge with OVA. Epicutaneously sensitized mice produced OVA-specific IgE and developed IgE-dependent anaphylaxis after oral challenge. Basophil-depleted or TSLP-receptor-deficient mice did not produce OVA-specific IgE and were protected from oral challenge-induced anaphylaxis. IL-33-deficient mice produced normal levels of OVA-specific IgE. However, IL-33-deficient mice and mice treated with recombinant soluble IL-33 receptor were protected from anaphylaxis. Thus, basophils and TSLP have pivotal roles in Th2 development in the skin during the sensitization phase of food allergy. In contrast, while IL-33 is dispensable for promoting cutaneous antigen sensitization, the cytokine is essential for inducing IgE-dependent anaphylaxis in the gut.